Moderna’s experimental Omicron booster generates high levels of antibodies that neutralize the BA.4 and BA.5 subvariants, according to preliminary clinical trial data.
- Omicron BA.4 and BA.5 subvariants become dominant forms of COVID-19 in Australia and overseas
- New data from Moderna shows an updated booster tailored to Omicron generates high levels of antibodies against BA.4 and BA.5
- Moderna’s chief medical officer says that, pending approval, the new booster could be delivered to Australia in August
These subvariants have established in the United States and Australiaand are already driving a new wave of infections in the UK.
Moderna’s results, which have not been peer-reviewed, build on an announcement made earlier this month that people receiving the new booster generally produced more antibodies to Omicron than if they received a fourth dose of the original vaccine.
Paul Burton, Moderna’s chief medical officer, said the trial participants’ antibody levels were high enough to provide “good clinical protection” against BA.4 and BA.5.
“We know that an antibody level of around 400 units…provides very good clinical protection against COVID infection, and certainly against more severe illness, hospitalization, and death,” he said. declared.
Of the 437 adults who had the Omicron-specific booster, those who had not yet had COVID generated mean BA.4 and BA.5 neutralizing antibody levels of 727 units after one month.
People who had already been infected with COVID saw a massive increase in neutralizing antibodies BA.4 and BA.5: more than 2,700 units.
Participants are being tracked to see if they end up catching COVID, and when.
University of Queensland infectious disease physician and clinical microbiologist Paul Griffin said neutralizing antibody responses was a good substitute for protection, but how well the booster worked was more important in the real world.
“Obviously it takes longer to accumulate this data, so it’s a useful first step, but clinical studies will follow that will hopefully show efficacy in people.”
A two-in-one COVID vaccine
The updated Moderna booster, called mRNA-1273.214, was developed in January, when Omicron was sweeping Australia.
The photo contains instructions in the form of mRNA for your body to build spike proteins – protrusions that the virus uses to infect our cells.
Your immune system then makes antibodies against various parts of the spike protein. If these antibodies again encounter spike proteins in the form of the real virus, they will recognize it and grab hold of it.
And if they squeeze the end of the spike, which is the part that clings to our cells, they neutralize it.
But if the tip protein changes too much, especially its capture end, this neutralizing power decreases.
To circumvent this, the new Moderna booster contains mRNA instructions for the spike protein of two viruses: the ancestral SARS-CoV-2 virus originating in Wuhan, as well as the Omicron BA.1 subvariant, which was circulating in January .
In the months that followed, other sub-variants of Omicron developed, with BA.4 and BA.5 now beginning to dominate new infections in many parts of the world.
BA.4 and BA.5 have the same set of genetic mutations in their spike protein, altering its shape slightly and allowing it to slip under the radar of the immune system and evade some of the antibodies we might have made against other variants – including antibodies produced upon infection with BA.1.
So how can a vaccine against two viruses – the original and Omicron BA.1 – make antibodies that neutralize a whole host of others?
This is a phenomenon called “epitope widening,” Dr. Burton said, something Moderna saw in trials of another variant-specific booster that included ancestral virus mRNA and beta variants.
“When you put two mRNAs together, and then two slightly different versions of the spike protein are produced in your body…you don’t just get antibodies against what you put. You get this really broad coverage of all kinds of new potential variations.
“If you now have Wuhan and Omicron, which are so far from the original Wuhan, and you put them together [in an mRNA vaccine]you can get very high levels of antibodies produced against BA.1, BA.2, BA.4 and 5, plus Delta and Beta and everything else.”
This, according to Magdalena Plebanski, a professor of immunology at RMIT University, is “the very good news”.
Omicron is not the latest COVID variant, and previous variants may reappear later.
“[The booster] is not just about tackling a new strain and then losing potency to previous strains,” Prof Plebanski said.
For the American and European autumn… and the Australian winter?
Moderna is submitting clinical trial data to an academic journal and is looking to roll out the updated booster for the Northern Hemisphere fall.
By then, BA.4 and BA.5 “will probably be a distant memory”, but the new booster will cover variants that have yet to appear, Dr Burton said.
“Our goal is also to be able to support Australia and its winter and to try, with the approval of the TGA and ATAGI, to deliver this candidate vaccine booster to Australia, even in August.”
The updated Moderna shot is a reasonable booster choice, Professor Plebanski said.
“And time is running out. At some point, our immunity [generated from third or fourth doses of COVID vaccine] will decrease.”
Dr. Griffin agreed. Variant-specific boosters are the way to go, he said, and they will be adjusted as needed, like the seasonal flu vaccine.
“But it’s not going to be as easy as some people might think right now, because we really have to think about the best time to use [a booster],” he said.
The message explaining why variant-specific boosters are needed will also need to be carefully considered to ensure sufficient and timely booster usage, Dr. Griffin added.
“It’s fine to develop this, but if we don’t deploy it quickly, it risks being redundant.
“And if the adoption isn’t high enough, it won’t have the impact that we need.”
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